Subtypes of serotonin receptors Seven major subtypes of serotonin receptor have been cloned so far. They differ in terms of pharmacological property, signal transduction mechanism, and gene sequence. The 5HT1a receptor is both a somatic autoceptor that controls the firing rate of 5HT neurons and a postsynaptic receptor. It thus closely governs mood regulation. The 5HT1b/d receptor is a terminal autoceptor, which controls the release of 5HT; however, its exact role in depression is still unclear. The 5HT2a-c receptor has been implicated in sleep, sex, and appetite regulation. The 5HT3 receptor is involved in the gratification response and drugabuse. The functions of other subtypes of receptors in psychiatric-related disorders remain to be investigated.

Key Brain regions and their hypothetical functions  Alterations in transmission of NT = Psychiatric disorders  Symptoms depend on which brain area is impaired  DA is dysregulated in schizophrenia = overactive, underactive or out of tune = -ve and +ve symptoms

ٍGlycine Level and Negative Symptoms in Schizophrenia Hani Hamed* Hesham Essa** Amr Zahra*** *Lecturer of Psychiatry and **Clinical Pathology, Beni-Suef University. ***Lecturer of Biochemistry, Al Fayoum University. Abstract: Objective: Previous studies have suggested that decreased N-methyl-D-aspartate (NMDA)-type glutamate receptor function may contribute to increased negative symptoms in patients with schizophrenia. Selective dysfunction or dysregulation of N-methyl-D-aspartate (NMDA)-type glutamate receptors may play a specific role in the pathophysiology of schizophrenia. Recent studies have investigated the ability of NMDA/glycine-site modulators to ameliorate persistent negative and cognitive symptoms. Method: Plasma levels of glycine, serine, and their ratio, were compared in 30 patientswith schizophrenia, and 30 age- and sex-matchednormal control subjects. All subjects were medication-free. Subjects in both groups were examined using the following tests: Familial Socioeconomic Status Scale, Global assessment of Function, Quality of life Scale, and Positive and Negative Syndrome Scale. Results: Plasma glycine level and glycine-serine ratio were lower in schizophrenic patients than in controlsubjects. Lower glycine level was correlated with a greater numberof negative symptoms. Shizophrenic patients showed lower quality of life. Conclusion: The decrease in plasma glycine level supports the evidence for an abnormality in the glutamatergic system in schizophrenia. The findings of this study support additional evidence that decreased glycine level in schizophrenic patients may be related to the pathophysiology of negative symptoms.

 In order to fully understand the properties of antipsychotics, it is imperative to examine the serotonin (5HT) pathways throughout the brain and how they modulate DA and glutamate circuits. Key Serotonin Pathways

 5HT1A is dopamine accelerator. However, 5HT2A is dopamine brake (opposite effect is on glutamate).

 Signal to noise ratio in schizophrenia could be related to deficit in filtration in information processing, too high, too low (out of tune), and chaotic theory.

The behavioral deficit state suggested by negative symptoms certainly implies underactivity or even "burnout" of neuronal systems. This may be related to the consequences of prior excitotoxic overactivity of glutamate systems

Basic Conclusion  Glutamate acts as accelerator on dop. in mesocortical area.  Glutamate acts as brake on dop. in mesolimbic area.  5HT 1A acts as accelerator on dop.  5HT2A acts as brake on dop.  5HT 1A acts as brake on glutamate.  5HT2A acts as accelerator on glutamate. So, atypical antipsychotics (mainly serotonergic, can decrease dopamine in mesolimbic area by 2 mechanisms 1st : it’s brake effect on dopamine through 5HT2A, and the 2nd is it’s accelerator effect on glutamate which is brake on dopamine).

 Inflammatory changes in schizophrenia  There is a growing body of evidence to suggest a role for inflammatory processes in schizophrenia. Research has shown that there are increased concentrations of pro-inflammatory cytokines, such as interleukin 6 and 8 (IL-6, IL-8) and tumour necrosis factor a (TNFa) in the serum of people with schizophrenia. The presence of a number of other markers of inflammation have also been demonstrated; for example, there is an increase in serum phospholiapse activity. In people with schizophrenia, the blood-cerebrospinal fluid (CSF) barrier is impaired and there is an increase in the concentration of serum intercellular cell adhesion molecule (sICAM) and immunoglobulin G (IgG) in the CSF. The activation of immune cells, such as monocytes and T- lymphocytes, and the production on the free radical NO are also indicators for the presence of an inflammatory process in schizophrenia.

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